DESCRIPTION [provided by applicant]: The University of Colorado Mental Retardation and Developmental Disabilities Research Center requests support for nine cores (eight previously funded and one proposed) for a comprehensive research program on MRDD. The research strengths of the Center encompass several themes. The first is studies in inborn errors of metabolism, including glutaric acidemic types I and II that were discovered at this Center, propronic academia, and homocystinuria. The second area of strength is in exploring the genes responsible for single and multigene disorders: autism, Down syndrome, fragile X syndrome, dyslexia, attention deficit hyperactivity disorder, and schizophrenia. A third group seeks to understand the phenotype and core deficits in very young children with autism and the inter-relationship between autism and fragile X syndrome. Determination of the neuropsychology of a variety of these disorders is a fourth strength of the proposed Center. The investigators will utilize a wide range of investigative techniques to approach these important problems, from studies of emotional development in humans, through the use of anatomic and behavioral studies of animal models, to very basic molecular understanding of gene regulation, to solving of the crystal structure of enzymes. The cores that support this research include Tissue Culture, Molecular Biology, Mass Spectrometry, Proteomics, and Analytical Chemistry, Developmental Neuropsychology, Animal Housing and Assessment, and Research Support Services. With the last funding cycle, the investigators initiated an Enzyme and Molecular Diagnosis Core that has been extremely successful in supporting the research of Center investigators. In addition, the investigators have started a new facility, the Human Subjects Recruitment and Evaluation Core. The Colorado Center has received substantial support from all levels of the University of Colorado and looks forward to a new era on a new campus, in which basic scientists, clinical investigators, and all clinical facilities will be united for the first time. An adjacent biotechnology park will facilitate the translation of Center findings into treatments. The investigators have been chosen to be in the first group of researchers to move to the new campus, and their space has been carefully designed to meet the needs as a center, and to put the Center investigator into proximity to other groups, such as Human Molecular Genetics, that can enhance Center scientific interactions. Strategic planning has led the investigators to initiate a series of hires, principally in basic neurosciences, and has led to considerable enhancement of cores.